Effect of a New Ultrashort Betalytic Agent on Aconitine-Induced Arrhythmia

Bartošová, Ladislava; Novák, Filip; Frydrych, Marek; Parák, Tomáš; Opatřilová, Radka; Brunclík, V.; Kolevská, J.; Moataz, Elnaggar El; Nečas, Jiří

doi:10.5507/bp.2005.054

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…Life-threatening cardiac arrhythmias were presented in all tested animals. Here, aconitine has a positive chronotropic effect, which is in line with observations of Bartosova et al (2007) (28). According to Sampson and Kass (2011), there are three major underlying mechanisms of cardiac arrhythmia: enhanced automaticity (SVPB, SVT, VPBS), triggered automaticity (PVT) and re-entry.…”

Section: Discussionsupporting

confidence: 83%

Antiarrhythmic effects of newly developed propafenone derivatives

Ivković¹,

Opačić²,

Džudović³

et al. 2022

Arhiv za farmaciju

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It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with -Cl or -F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects.

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Section: Discussionsupporting

confidence: 83%

Antiarrhythmic effects of newly developed propafenone derivatives

Ivković¹,

Opačić²,

Džudović³

et al. 2022

Arhiv za farmaciju

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“…Recording the lead II ECGs for 20 min prior to administration, then the experimental compounds, positive drugs, and equal volume of saline were subsequently administered via the exposed vena femoral, respectively. After stabilization for 10 min [ 21 ], aconitine was administered into the vena femoral at a dosage of 0.03 mg/kg [ 22 – 24 ] to establish arrhythmia ( Figure 1 ). The onset time of VPB [ 25 ] was recorded within 30 min [ 25 – 27 ] after aconitine injection.…”

Section: Methodsmentioning

confidence: 99%

Attenuated Structural Transformation of Indaconitine during Sand Frying Process and Anti-Arrhythmic Effects of Its Transformed Products

Pei

Wang

2022

Evidence-Based Complementary and Alternative Medicine

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The transformation pathways of diterpenoid alkaloids have been clarified clearly in the boiling and steaming process, but remain to be determined in the sand frying process. The aims of the study were to investigate the transformation pathways of indaconitine in the sand frying process, as well as examine the cardiotoxicity and anti-arrhythmic activity of indaconitine and its transformed products. The transformed product was separated by column chromatography, and the structure was identified by 1H NMR, 13C NMR, and HR-ESI-MS. The cardiotoxicity of indaconitine and its transformed products was clarified by observing the electrocardiogram (ECG) changes at the same dose. Furthermore, the anti-arrhythmic activity of the transformed products was investigated using an aconitine-induced rat arrhythmia model. Consequently, Δ15(16)-16-demethoxyindaconitine, a new diterpenoid alkaloid, was isolated from processed indaconitine. Intravenous injection of 0.06 mg/kg indaconitine induced arrhythmias in SD rats, while Δ15(16)-16-demethoxyindaconitine did not exhibit arrhythmias at the same dose. In the anti-arrhythmic assay, mithaconitine, obtained in the previous research, together with Δ15(16)-16-demethoxyindaconitine, could dose-dependently delay the onset time of ventricular premature beat (VPB) and reduce the incidence of ventricular tachycardia (VT), combined with the increasing arrhythmia inhibition rate, exhibiting strong anti-arrhythmic activities. These results indicated that two or more pathways exist in the sand frying process, and the transformed products exhibited lower cardiotoxicity and strong anti-arrhythmic activities, which had the possibility of being developed into anti-arrhythmic drugs.

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“…Recording the lead II ECGs for 20 min prior to administration, the experimental compounds, positive drugs, and equal volume of saline were subsequently administered via the exposed vena femoral, respectively. After stabilization for 10 min ( Zhang et al, 2006 ), aconitine was administered into the uncovered vena femoral at a dosage of 0.03 mg/kg ( Bartosová et al, 2005 ; Klekot, 2006 ; Bartosova et al, 2007 ) to establish arrhythmia ( Figure 1 ). The onset time of VPB ( Qiu et al, 2016 ) was recorded within 30 min ( Sun et al, 2006 ; Zhang and Xiong, 2015 ; Qiu et al, 2016 ) after aconitine.…”

Section: Methodsmentioning

confidence: 99%

Attenuation and Structural Transformation of Crassicauline A During Sand Frying Process and Antiarrhythmic Effects of its Transformed Products

Pei

Wang

2021

Front. Pharmacol.

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To ensure safety and efficacy, most Aconitum herbs should be processed before clinical application. The processing methods include boiling, steaming, and sand frying. Among these methods, the transformation pathways of diterpenoid alkaloids in the process of sand frying are more complicated. Therefore, crassicauline A, a natural product with two ester bonds, was chosen as the experimental object. Consequently, a known alkaloid, together with three new alkaloids, was derived from crassicauline A. Meanwhile, the cardiotoxicity of converted products was reduced compared with their parent compound. Interestingly, some diterpenoid alkaloids have similar structures but opposite effects, such as arrhythmia and antiarrhythmic. Considering the converted products are structural analogues of crassicauline A, herein, the antiarrhythmic activity of the transformed products was further investigated. In a rat aconitine-induced arrhythmia assay, the three transformed products, which could dose-dependently delay the ventricular premature beat (VPB) incubation period, reduce the incidence of ventricular tachycardia (VT), combined with the increasing arrhythmia inhibition rate, exhibited prominent antiarrhythmic activities. Our experiments speculated that there might be at least two transformation pathways of crassicauline A during sand frying. The structure-activity data established in this paper constructs the critical pharmacophore of diterpenoid alkaloids as antiarrhythmic agents, which could be helpful in searching for the potential drugs that are equal or more active and with lower toxicity, than currently clinical used antiarrhythmic drugs.

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Effect of a New Ultrashort Betalytic Agent on Aconitine-Induced Arrhythmia

Cited by 5 publications

References 13 publications

Antiarrhythmic effects of newly developed propafenone derivatives

Antiarrhythmic effects of newly developed propafenone derivatives

Attenuated Structural Transformation of Indaconitine during Sand Frying Process and Anti-Arrhythmic Effects of Its Transformed Products

Attenuation and Structural Transformation of Crassicauline A During Sand Frying Process and Antiarrhythmic Effects of its Transformed Products

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